Log in

Effects of tanshinone IIA on transforming growth factor β1-Smads signal pathway in renal interstitial fibroblasts of rats

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

The effects of tanshinone IIA (TSN) on transforming growth factor β1 (TGFβ1) signal transduction in renal interstitial fibroblasts of rats were studied in order to investigate its mechanism in prevention of renal interstitial fibrosis. Rat renal fibroblasts of the line NRK/49F were cultured in vitro, stimulated with 5 ng/mL TGFβ1 and pretreated with 10−6, 10−5, 10−4 mol/L TSN respectively. The mRNA levels of fibronectin (FN) were examined by RT-PCR. The protein expression of FN and Smads was detected by Western blot. TGFβ1 induced the expression of FN mRNA and Smads in a time-dependent manner in a certain range. Compared with pre-stimulation, the FN mRNA and protein levels were increased by 1.1 times and 1.5 times respectively (P<0.01, P<0.01), and the protein expression of phosphorylated Smad2/3 (p-Smad2/3) increased by 7 times at the end of TGFβ1 stimulation (P<0.01). TSN pretreatment may down-regulate the FN and p-Smad2/3 expression in a dose-dependent manner. 10−6 mol/L TSN pretreatment had no effect on the FN and p-Smad2/3 expression (both P>0.05). After pretreatment with 10−5 and 10−4 mol/L TSN, the FN mRNA levels were decreased by 28.1% and 43.8% respectively (P<0.05, P<0.01), the FN protein levels were decreased by 40% and 44% respectively (P<0.05, P<0.05), and the p-Smad2/3 protein expression were decreased by 40% and 65% respectively (P<0.05, P<0.01). The inhibitory effect of TSN on renal interstitial fibrosis may be related to its blocking effect on TGFβ1-Smads signal pathway in renal interstitial fibroblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Catania J M, Chen G, Parrish A R. Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol, 2007,292(3):F905–F911

    Article  PubMed  CAS  Google Scholar 

  2. Iwano M, Neilson E G. Mechanisms of tubulointerstitial fibrosis. Curr Opin Nephrol Hypertens, 2004,13(3):279–284

    Article  PubMed  Google Scholar 

  3. Gaedeke J, Peters H, Noble N A et al. Angiotensin II, TGF-beta and renal fibrosis. Contrib Nephrol, 2001,13(5):153–160

    Article  Google Scholar 

  4. Okada H, Kalluri R. Cellular and molecular pathways that lead to progression and regression of renal fibrogenesis. Curr Mol Med, 2005,5(5):467–474

    Article  PubMed  CAS  Google Scholar 

  5. Li J, Campanale N V, Liang R J et al. Inhibition of p38 mitogen-activated protein kinase and transforming growth factor-beta1/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy. Am J Pathol, 2006,169(5):1527–1540

    Article  PubMed  CAS  Google Scholar 

  6. Wu S H, Lu C, Dong L et al. Lipoxin A4 induced renal interstitial fibroblast apoptosis by up-regulating Smad expression. Chin J Nephrol (Chinese), 2004,20(5):339–342

    Google Scholar 

  7. Leask A, Abraham D J. TGF-beta signaling and the fibrotic response. FASEB J, 2004,18(7):816–827

    Article  PubMed  CAS  Google Scholar 

  8. Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int, 2006,69(2):213–217

    Article  PubMed  CAS  Google Scholar 

  9. Yang W F, Cheng H C, **a B J. Effect of Tanshinone IIA on HSC proliferation and ECM secretion. J Prac Med (Chinese), 2003,19(11):2126–2128

    Google Scholar 

  10. Hua H Y, Guo X G, Yang B et al. Effect of sodium Tanshinone IIA sulfonate on human HSC. Pharmacol Clin Chin Material Med (Chinese), 2007,23(6):12–14

    CAS  Google Scholar 

  11. **e H, Zhen Z, Gong L Y. Effect of Tanshinone IIA on left ventricular hypertrophy of rats with spontaneous hypertension and its mechanism. J Prac Med (Chinese), 2004,20(3):258–260

    Google Scholar 

  12. Tang X Z, Zhen Z, Tang Y et al. Reversal effect of Tanshinone IIA on cardiac fibrosis of rats with spontaneous hypertension and its mechanism. J Huazhong Univ Sci Technol [Med Sci], 2002,31(3):292–294.

    CAS  Google Scholar 

  13. Sun X W, Cao L, Yu G H et al. Effect of sodium Tanshinone IIA sulfonate on proliferation and cyclin E expression in human renal interstitial fibroblasts in vitro. Acta Acad Med Mil Tertiae (Chinese), 2007,29(7):585–587

    CAS  Google Scholar 

  14. Tang J H, Zhan C Y. Inhibitive effect of Tanshinone IIA on renal interstitial fibrosis in rats. J Inter Intens Med (Chinese), 2008,14(1):16–18

    Google Scholar 

  15. Li N J, Li H. Effect of TGF-β/Smad signal transduction in renal fibrosis. Int J Urol Nephrol (Chinese), 2007,27(1):88–91

    Google Scholar 

  16. Wang W, Koka V, Lan H Y. Transforming growth factor-beta and Smad signaling in kidney diseases. Nephrology, 2005,10(1):48–56

    Article  PubMed  Google Scholar 

  17. Stahl P J, Felsen D. Transforming growth factor-beta, basement membrane, and epithelial-mesenchymal trans-differentiation: implications for fibrosis in kidney disease. Am J Pathol, 2001,159(4):1187–1192

    PubMed  CAS  Google Scholar 

  18. Verrecchia F, Mauviel A. Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol, 2002,118(2):211–215

    Article  PubMed  CAS  Google Scholar 

  19. Mao Y, Schwarzbauer J E. Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol, 2005,24(6):389–399

    Article  PubMed  CAS  Google Scholar 

  20. Kiribayashi K, Masaki T, Naito T et al. Angiotensin II induces fibronectin expression in human peritoneal mesothelial cells via ERK1/2 and p38 MAPK. Kidney Int, 2005,67(3):1126–1135

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This project was supported by a grant from Hubei Natural Science Foundation of China (No.2007ABA272).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tang, J., Zhan, C. & Zhou, J. Effects of tanshinone IIA on transforming growth factor β1-Smads signal pathway in renal interstitial fibroblasts of rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 28, 539–542 (2008). https://doi.org/10.1007/s11596-008-0511-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-008-0511-0

Key words

Navigation